This project is a quantitative light & electron microscopic study of the development of neuronal circuitry in cerebral cortex, particularly of the spatial and temporal aspects of synapse formation. The major goal is to obtain quantitative parameters of normal development in human, dog, and rodent; equivalent stages will be determined in different species, and thereby data from experimental animal studies will be more applicable to human development. The strategy is first to determine the radial distribution of synapses in immature cortex and then to identify the pre- and post-synaptic elements. Histograms of synaptic density as a function of subpial depth will be determined in newborn rats and mice. Serial section analysis with electron microscopy will aid in the identification of post-synaptic cells. The adult fate of post-synaptic newborn cells is determined by triated thymidine autoradiography and, thus, the layer of cortex where early synapses are formed (i.e., in neonate) will be identified with regard to its adult status. A detailed analysis of human cortex development will be completed (both cytoarchitectonic and synapse development). The location of cells of origin (?thalamus) of deep cortical synapses in the newborn rat will be studied using microiontophoresis of horseradish peroxidase into neocortex. The patterns of synapse and layer development will be compared in cortes of different species.